Enhanced Angiogenic Potential of Electrically Stimulated Human Adipose-Derived Mesenchymal Stem Cells (MSCs) for Ischemic Tissue Regeneration

Abstract

Effective treatment of ischemic disease requires the reconstruction of blood vessels through the delivery of angiogenic factors, such as chemicals, proteins, and cells. In particular, substantial efforts have focused on enhancing the therapeutic potential of mesenchymal stem cells (MSCs) for treating ischemic diseases. In this study, we investigated the use of electrical stimulation (ES) to potentiate the proangiogenic properties of human adipose-derived MSCs. Electrically potentiated MSCs (epMSCs) were generated by applying optimized ES parameters (0.3 V, 100 Hz). EpMSCs exhibited significantly enhanced angiogenic potential, including upregulated expression of proangiogenic factors (e.g., vascular endothelial growth factor [VEGF]-A and hepatocyte growth factor) and improved endothelial cell migration and tube formation in vitro. Transcriptomic and proteomic analyses revealed activation of key angiogenic pathways, particularly VEGFA–VEGFR2 signaling, which plays a critical role in enhancing the functionality of epMSCs. In vivo studies using a murine hindlimb ischemia model demonstrated that epMSCs enhanced blood flow recovery, induced angiogenesis, and reduced muscle atrophy more effectively than unstimulated MSCs. Overall, these findings suggest that electrical potentiation of MSCs is a promising strategy for effectively enhancing their angiogenic capabilities for treating ischemic diseases.